For water containing aqueous external preparations, ointments, lotions, aqueous plasters, and the like have been proposed up to now. Among these external preparations, ointments and lotions have been considered less suitable for administration of an active ingredient containing therein continuously and in constant dosages and are also thought to be inconvenient since they may stick elsewhere other than the intended application site, and may sometimes soil the clothes at the time of administration.
Further, an aqueous plaster, though not associated with these problems, has a low adhesiveness and thus requires fixing means such as a strip of surgical tape so that it stays on flextion parts such as elbows and knees.
On the other hand, there has been non-aqueous adhesives preparation using natural or synthetic rubber as a base material or plaster using adhesive acrylate type resin as base material. These types of preparations have a strong adhesiveness and are thought to overcome the drawbacks of aqueous plasters.
However, it is difficult to dissolve an active ingredient in the non-aqueous adhesive base material when said active ingredient hardly dissolves in polyols, glycols, and esters, which are commonly used as a solvent for external plasters. Especially, addition of water-soluble drug causes many problems such as appearance of crystalline of the drugs in the base material, low percutaneous absorption of the drugs, and so on due to the low solubility of said drugs
To solve these problems, for example, there has been proposed to use crotamiton as a solubilizer for the drugs in Japanese Patent Laid-Open Publication No. Hei 4-321624. However, it has been difficult heretofore, even with the help of the solubilizer, to obtain the non-aqueous adhesive base material that contains drugs in an amount sufficient to allow it to exert desired pharmacological effects.
By the way, in the case of aqueous plasters containing a water-soluble drug, the drug is solubilized in the adhesive base material by ionizing with an organic aqueous amine compound such as diisopropanol amine, when the drug is an acidic compound. Though possible, adoption of this technique in producing non-aqueous adhesives preparation containing the water-soluble drug, for example, solvent adhesives, which require a drying process, or hot melted type adhesive base materials, which require exposure to high temperature, may result in evaporation of moisture and thus crystallization of the drug in the adhesive base.
A surfactant may also be used as a component of the hot melted type adhesive base material in order to facilitate mixing of water. This approach, however, may cause skin irritation and thus is not favorable.
Aside from the above-described approaches, a water-absorbable or water-soluble high molecular weight compound is thought to enable the adhesive material to absorb water. One disadvantage of this approach is that moisture evaporates when the temperature is raised to melt the successive adhesive in continuous production. As a result, the high molecular weight compound crystallizes and forms unwanted particles in the adhesive base. Moreover, water is surrounded by the high molecular weight compound which is presented in the adhesive base material, and this prevents diffusion of the drug, i.e., the active ingredient, in the adhesive preparation, and as a result, the efficiency of the drug utilization is lowered.
Accordingly, it is an objective of the present invention to provide external plasters using an aqueous hot melted type adhesive base material which stably contains the active ingredient and exhibits a good releasability of the drug from the adhesive base material, thereby enhancing bioavailability of the drug based on the percutaneous absorption.